Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Sialic acid is a critical fetal defense against maternal complement attack
Markus Abeln, … , Anja Münster-Kühnel, Birgit Weinhold
Markus Abeln, … , Anja Münster-Kühnel, Birgit Weinhold
Published November 1, 2018
Citation Information: J Clin Invest. 2019;129(1):422-436. https://doi.org/10.1172/JCI99945.
View: Text | PDF
Research Article Immunology Reproductive biology

Sialic acid is a critical fetal defense against maternal complement attack

  • Text
  • PDF
Abstract

The negatively charged sugar sialic acid (Sia) occupies the outermost position in the bulk of cell surface glycans. Lack of sialylated glycans due to genetic ablation of the Sia-activating enzyme CMP–sialic acid synthase (CMAS) resulted in embryonic lethality around day 9.5 post coitum (E9.5) in mice. Developmental failure was caused by complement activation on trophoblasts in Cmas–/– implants and was accompanied by infiltration of maternal neutrophils at the fetal-maternal interface, intrauterine growth restriction, impaired placental development, and a thickened Reichert’s membrane. This phenotype, which shared features with complement receptor 1-related protein Y (Crry) depletion, was rescued in E8.5 Cmas–/– mice upon injection of cobra venom factor, resulting in exhaustion of the maternal complement component C3. Here we show that Sia is dispensable for early development of the embryo proper but pivotal for fetal-maternal immune homeostasis during pregnancy, i.e., for protecting the allograft implant against attack by the maternal innate immune system. Finally, embryos devoid of cell surface sialylation suffered from malnutrition due to inadequate placentation as a secondary effect.

Authors

Markus Abeln, Iris Albers, Ulrike Peters-Bernard, Kerstin Flächsig-Schulz, Elina Kats, Andreas Kispert, Stephen Tomlinson, Rita Gerardy-Schahn, Anja Münster-Kühnel, Birgit Weinhold

×

Figure 4

Depletion of maternal neutrophils does not rescue the Cmas–/– phenotype.

Options: View larger image (or click on image) Download as PowerPoint
Depletion of maternal neutrophils does not rescue the Cmas–/– phenotype....
(A) Neutrophils were depleted by intraperitoneal injection of 500 μg anti-Ly6G antibody (1A8, BioXCell) into pregnant mice at E4.5. Ly6G FACS analysis of whole blood from untreated and anti-Ly6G–injected pregnant mice at day E8.5. (B) Ly6G (neutrophils) immunohistochemical staining of sagittal paraffin sections of embryos within the uterus. Pregnant females were either treated with the isotype antibody (2A3, BioXCell) as a negative control or with anti-Ly6G for neutrophil depletion. Representative images of control (n = 6) and Cmas–/– (n = 4) embryos. (C) Mean fetal size of control and Cmas–/– embryos from anti-Ly6G–treated mother mice, as measured by the sum of the areas of the amniotic cavity, exocoelomic cavity, ectoplacental cavity, and embryo proper (μm2/105) (control, n = 6; Cmas–/–, n = 4). For a schematic overview of the measured areas, see Supplemental Figure 5. Error bars indicate SD. Statistical analyses were performed by Student’s t test (**P < 0.01). (D) Immunohistochemical detection of cytokeratin-8 to visualize trophoblast cells on sagittal paraffin sections of E8.5 uteri from Ly6G-treated mother mice. Representative images of control (n = 6) and Cmas–/– (n = 4) embryos. (E) Collagen IV indirect immunofluorescence staining on sagittal paraffin sections of uteri at E8.5 from Ly6G-treated mother mice to visualize RM (arrow) and parietal endoderm (arrowheads). Representative images of control (n = 6) and Cmas–/–(n = 4) embryos. Nuclei stained with DAPI are shown in white.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts